CN113861053A - Preparation method of tri (hydroxymethyl) methylglycine - Google Patents
Preparation method of tri (hydroxymethyl) methylglycine Download PDFInfo
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- CN113861053A CN113861053A CN202111129423.XA CN202111129423A CN113861053A CN 113861053 A CN113861053 A CN 113861053A CN 202111129423 A CN202111129423 A CN 202111129423A CN 113861053 A CN113861053 A CN 113861053A
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- compound
- acid
- reaction
- hydroxymethyl
- methylglycine
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- 238000002360 preparation method Methods 0.000 title claims abstract description 86
- LOTVQXNRIAEYCG-UHFFFAOYSA-N 3-hydroxy-2-(hydroxymethyl)-2-[hydroxymethyl(methyl)amino]propanoic acid Chemical compound OCN(C)C(CO)(CO)C(O)=O LOTVQXNRIAEYCG-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 238000006243 chemical reaction Methods 0.000 claims abstract description 67
- SEQKRHFRPICQDD-UHFFFAOYSA-N Tricine Natural products OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 claims abstract description 54
- 229940126062 Compound A Drugs 0.000 claims abstract description 37
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims abstract description 37
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 239000012043 crude product Substances 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 14
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 238000001035 drying Methods 0.000 claims description 35
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 claims description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 25
- 238000001914 filtration Methods 0.000 claims description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 230000035484 reaction time Effects 0.000 claims description 18
- 239000007810 chemical reaction solvent Substances 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 claims description 10
- 238000000746 purification Methods 0.000 claims description 10
- 150000008064 anhydrides Chemical class 0.000 claims description 8
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 8
- -1 amine cation Chemical class 0.000 claims description 7
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 7
- 229940106681 chloroacetic acid Drugs 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 6
- FYFFGSSZFBZTAH-UHFFFAOYSA-N methylaminomethanetriol Chemical compound CNC(O)(O)O FYFFGSSZFBZTAH-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- FHHJDRFHHWUPDG-UHFFFAOYSA-N peroxysulfuric acid Chemical compound OOS(O)(=O)=O FHHJDRFHHWUPDG-UHFFFAOYSA-N 0.000 claims description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 3
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 3
- 229920002866 paraformaldehyde Polymers 0.000 claims description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-M 3-chlorobenzoate Chemical compound [O-]C(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-M 0.000 claims description 2
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 2
- JXASPPWQHFOWPL-UHFFFAOYSA-N Tamarixin Natural products C1=C(O)C(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(CO)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 JXASPPWQHFOWPL-UHFFFAOYSA-N 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical class OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 claims description 2
- 150000007942 carboxylates Chemical class 0.000 claims description 2
- 229910001919 chlorite Inorganic materials 0.000 claims description 2
- 229910052619 chlorite group Inorganic materials 0.000 claims description 2
- 229940077239 chlorous acid Drugs 0.000 claims description 2
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 claims description 2
- CMMUKUYEPRGBFB-UHFFFAOYSA-L dichromic acid Chemical compound O[Cr](=O)(=O)O[Cr](O)(=O)=O CMMUKUYEPRGBFB-UHFFFAOYSA-L 0.000 claims description 2
- VFNGKCDDZUSWLR-UHFFFAOYSA-N disulfuric acid Chemical compound OS(=O)(=O)OS(O)(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-N 0.000 claims description 2
- 229940075933 dithionate Drugs 0.000 claims description 2
- RMGVZKRVHHSUIM-UHFFFAOYSA-N dithionic acid Chemical compound OS(=O)(=O)S(O)(=O)=O RMGVZKRVHHSUIM-UHFFFAOYSA-N 0.000 claims description 2
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 claims description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 claims description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 150000002978 peroxides Chemical class 0.000 claims description 2
- FHHJDRFHHWUPDG-UHFFFAOYSA-L peroxysulfate(2-) Chemical compound [O-]OS([O-])(=O)=O FHHJDRFHHWUPDG-UHFFFAOYSA-L 0.000 claims description 2
- 238000010926 purge Methods 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims 2
- 150000001768 cations Chemical class 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 34
- 239000006177 biological buffer Substances 0.000 abstract description 9
- 239000012535 impurity Substances 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 abstract 2
- 238000001816 cooling Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 238000002390 rotary evaporation Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 239000002585 base Substances 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 6
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 2
- 239000007997 Tricine buffer Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 2
- 238000007400 DNA extraction Methods 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- SESSOVUNEZQNBV-UHFFFAOYSA-M sodium;2-bromoacetate Chemical compound [Na+].[O-]C(=O)CBr SESSOVUNEZQNBV-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of biological buffers, and discloses a preparation method of tri (hydroxymethyl) methylglycine, which comprises the following preparation steps: reacting the compound I with the compound A to obtain a compound II; and (3) carrying out at least one of hydrolysis reaction, oxidation reaction and acid-base treatment reaction on the compound II to obtain a crude product of the tris (hydroxymethyl) methylglycine, and purifying to obtain a refined product of the tris (hydroxymethyl) methylglycine. The preparation method disclosed by the invention has the advantages that the cost of the raw materials used in the preparation method is low, the operation is simple, the purity of the obtained product is higher, the yield of the product is improved, the application cost of the product is reduced, the obtained product meets the requirements of the biological buffer agent field on the purity, the impurity content, the cost and the like, and the method is suitable for industrial production and is suitable for application in the biological buffer agent field.
Description
Technical Field
The invention relates to the technical field of biological buffers, in particular to a preparation method of tri (hydroxymethyl) methylglycine.
Background
Tris (hydroxymethyl) methylglycine, Tricine for short, CAS 5704-04-1, is a zwitterionic buffer used in biochemistry and molecular biology. Tricine has pH buffer range of 7.4-8.8, is mainly used for substituting glycine, and is applied to small molecule protein electrophoresis in cooperation with SDS (sodium dodecyl sulfate); in biochemical research, the method is commonly used in biochemical diagnostic kits, DNA/RNA extraction kits and PCR diagnostic kits.
Patent CN112194590A discloses a method for preparing tris (hydroxymethyl) methylglycine, which comprises reacting sodium chloroacetate and tris (hydroxymethyl) aminomethane in methanol, controlling the pH value within the range of 8-10, then cooling, adding concentrated sulfuric acid, crystallizing, drying and the like to obtain tris (hydroxymethyl) methylglycine. The preparation method has the defects of strict control of reaction conditions, complex preparation process, low product purity, high product impurity and the like. Therefore, it is highly desirable to provide a method for preparing tris (hydroxymethyl) methylglycine with simple production method, high product purity and high yield.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the preparation method of the tris (hydroxymethyl) methylglycine, the raw materials used in the preparation method are low in cost, the operation is simple, the yield of the prepared product is high, the crude tris (hydroxymethyl) methylglycine obtained by the preparation method is purified to obtain the refined tris (hydroxymethyl) methylglycine with high purity, and the requirements of the biological buffer agent field on the purity, the impurity content, the cost and the like of the refined tris (hydroxymethyl) methylglycine are met.
The invention is realized by adopting the following technical scheme:
a preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1: reacting the compound I with the compound A to obtain a compound II;
preparation step S2: carrying out at least one reaction of hydrolysis reaction, oxidation reaction and acid-base treatment reaction on the compound II to obtain tri (hydroxymethyl) methylglycine;
the acid-base treatment reaction comprises at least one of acid treatment and alkali treatment;
wherein, the compound I is trihydroxymethyl aminomethane;
the compound A is
Or a salt thereof,
Or a salt thereof,
Or a salt thereof,
Y is halogen, OH, SH, ester corresponding to OH and ester corresponding to SH.
Preferably, the compound A is
At least one of, the Y1、Y2Are halogen, OH, SH, esters corresponding to OH, esters corresponding to SH;
preferably, the compound A is at least one of bromoacetic acid, an ester corresponding to bromoacetic acid, an acid anhydride corresponding to bromoacetic acid, a mixed acid anhydride corresponding to bromoacetic acid, a bromoacetate salt, iodoacetic acid, an ester corresponding to iodoacetic acid, an acid anhydride corresponding to iodoacetic acid, a mixed acid anhydride corresponding to iodoacetic acid, and an iodoacetate salt.
Preferably, the compound A is at least one of ester corresponding to chloroacetic acid, anhydride corresponding to chloroacetic acid and mixed anhydride corresponding to chloroacetic acid.
Preferably, the compound A is at least one of formaldehyde, paraformaldehyde, cyanuric acid and cyanide MCN, and N is one of metal positive ions, inorganic ammonium positive ions and organic amine positive ions.
The reaction equation of the preparation step S1 is shown by the following formula (1):
the reaction equation of the preparation step S2 is shown in the following formula (2):
preferably, the ester mentioned in the compound A is at least one of carboxylate, sulfonate, sulfinate and inorganic acid ester.
Preferably, the salt mentioned in the compound A is at least one of metal salt, ammonium salt and complex salt based on acid-base action.
Preferably, in the preparation step S2, the oxidizing agent used in the oxidation reaction of the compound II is at least one of peroxide, ozone, permanganic acid, permanganate, dichromic acid, dichromate, hypochlorous acid, hypochlorite, chlorous acid, chlorite, fluorine gas, a fluorine-containing gas mixture, chlorine gas, bromine, iodine, manganese dioxide, nitric acid, m-chlorobenzoic acid, m-chlorobenzoate, sulfuric acid, peroxymonosulfuric acid, peroxymonosulfate, dithionic acid, dithionate, pyrosulfuric acid, pyrosulfate, oxygen, caro acid, m-chloroperoxybenzoic acid, m-chloroperoxybenzoate, sulfur dioxide, and nitrogen dioxide.
Preferably, in the preparation step S1, the molar ratio of compound I to compound a is 1: (0.1 to 10); in preparation step S2, the molar ratio of compound II to oxidizing agent is 1: (0.1-10).
Preferably, in the preparation step S1, the reaction temperature is-50 ℃ to 200 ℃, the reaction pressure is-0.05 MPa to 1MPa, and the reaction time is 0.1h to 72 h; in the preparation step S2, the reaction temperature is-50 ℃ to 200 ℃, the reaction pressure is-0.05 MPa to 1MPa, and the reaction time is 0.1h to 72 h.
Preferably, in the preparation step S1, compound I is reacted with compound a in a reaction solvent a, wherein the reaction solvent a is at least one of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, water, and dimethyl sulfoxide; in the preparation step S2, the compound II is reacted in a reaction solvent B, which is at least one of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, water, and dimethyl sulfoxide.
The preparation method of the tri (hydroxymethyl) methylglycine further comprises the following preparation steps:
under a dry condition, the crude tris (hydroxymethyl) methylglycine obtained in the preparation step S2 is dissolved in a purification solvent by using a dry closed device or under dry gas purging, and then recrystallization is performed, followed by crystallization, filtration and drying under a low temperature condition, so as to obtain the refined tris (hydroxymethyl) methylglycine.
The purifying solvent is at least one of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, water and dimethyl sulfoxide.
Compared with the prior art, the invention has the beneficial effects that:
the preparation method disclosed by the invention has the advantages that the cost of the raw materials used in the preparation method is low, the operation is simple, the purity of the obtained product is higher, the yield of the product is improved, the application cost of the product is reduced, the obtained product meets the requirements of the biological buffer agent field on the purity, the impurity content, the cost and the like, and the method is suitable for industrial production and is suitable for application in the biological buffer agent field.
According to the preparation method, the compound I which is easy to obtain and low in cost is selected to react with the compound A to generate the compound II, and then the compound II is subjected to hydrolysis reaction, oxidation reaction, acid-base treatment reaction and other reactions to obtain the tri (hydroxymethyl) methylglycine.
The product obtained by the preparation process is easy to purify and separate, and by-products and impurities generated in the reaction process can meet the application standard of the field of biological buffers on high purity, so that the requirements of various aspects of large-scale production and application are met.
The whole preparation process is simple and easy to control, is favorable for enlarging production, shortens the reaction production period, can obtain the tri (hydroxymethyl) methylglycine with higher purity through conventional recrystallization purification, and can effectively improve the yield of the product.
Detailed Description
The present invention is further described below with reference to specific embodiments, and it should be noted that, without conflict, any combination between the embodiments or technical features described below may form a new embodiment. It is noted that the terminology used in the examples is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention. In addition, the raw materials used in the invention are all common commercial products, so that the sources of the raw materials do not need to be particularly limited.
The pressure values mentioned in the present invention are, if not specified otherwise, gauge pressures, which are the total absolute pressure exceeding the ambient atmospheric pressure or the pressure at a point in the liquid above atmospheric pressure.
The yield is the percentage ratio of the actual product mass to the theoretical product mass, which is calculated with no excess of starting materials in the reaction equation.
In the following examples, the test methods: nuclear magnetic analysis testing using an AVANCE 400 mega nuclear magnetic resonance spectrometer from Bruker (Bruker); the purity of the product was determined by an acid-base titrator.
Example 1
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of compound I, trihydroxymethyl aminomethane, compound A and reaction solvent ethanol are added into a 1L drying reactor, the molar ratio of the compound I to the compound A is 1:1 respectively, the temperature of a reaction oil bath is 60 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 4 h.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein the compound A is
Y is Cl.
Preparation step S2:
under the condition of stirring, 20g of a compound II and a reaction solvent ethanol are added into a 1L drying reactor, an oxidation reagent hydrogen peroxide is added, the molar ratio of the compound II to the oxidation reagent is 1:3 respectively, the temperature of a reaction oil bath is 65 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 6 h.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 90%.
Preparation step S3:
under the drying condition, the tris (hydroxymethyl) methylglycine of the crude product obtained in the preparation step S2 is dissolved in a purification solvent ethanol by using a drying closed device, then recrystallization is carried out, crystallization, filtration and drying are carried out under the low temperature condition, and the refined tris (hydroxymethyl) methylglycine refined product with the purity of 99.5 percent is obtained.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
example 2
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of compound I, tris (hydroxymethyl) aminomethane, compound A and a reaction solvent methanol were added into a 1L dry reactor, the molar ratio of compound I to compound A was 1:1.05, the reaction oil bath temperature was 60 ℃, the reaction pressure was 0.01MPa (gauge pressure), and the reaction time was 4 hours.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein the compound A is
Y is OH.
Preparation step S2:
under the condition of stirring, 20g of compound II and a reaction solvent methanol are added into a 1L drying reactor, hydrolysis reaction and acid-base treatment are carried out on the compound II and water, the temperature of a reaction oil bath is 94 ℃, the reaction pressure is 0.015MPa (gauge pressure), and the reaction time is 6 h.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 93%.
Preparation step S3:
under the drying condition, the tris (hydroxymethyl) methylglycine of the crude product obtained in the preparation step S2 is dissolved in a purification solvent ethanol by using a drying closed device, then recrystallization is carried out, crystallization, filtration and drying are carried out under the low temperature condition, and the refined tris (hydroxymethyl) methylglycine refined product with the purity of 99.6 percent is obtained.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
example 3
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of compound I, trihydroxymethyl aminomethane, compound A and reaction solvent acetonitrile are added into a 1L drying reactor, the molar ratio of the compound I to the compound A is respectively 1:2, the temperature of a reaction oil bath is 60 ℃, the reaction pressure is-0.01 MPa (gauge pressure), and the reaction time is 4 h.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein the compound A is
Y is Br.
Preparation step S2:
under the condition of stirring, 20g of compound II and acetonitrile serving as a reaction solvent are added into a 1L drying reactor, water is added, hydrolysis reaction is carried out on the compound II and the water, the temperature of a reaction oil bath is 90 ℃, the reaction pressure is 0.02MPa (gauge pressure), the reaction time is 6h, and acid-base treatment reaction is carried out.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 94%.
Preparation step S3:
under the drying condition, the tris (hydroxymethyl) methylglycine of the crude product obtained in the preparation step S2 is dissolved in a purification solvent acetonitrile by using a drying closed device, then recrystallization is carried out, crystallization, filtration and drying are carried out under the low temperature condition, and the refined tris (hydroxymethyl) methylglycine refined product with the purity of 99.7 percent is obtained.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
example 4
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of a mixture of compound I, tris (hydroxymethyl) aminomethane, compound A, a reaction solvent ethanol and water was added to a 1L dry reactor, the molar ratio of compound I to compound A was 1:4, the reaction oil bath temperature was 60 ℃, the reaction pressure was 0MPa (gauge pressure), and the reaction time was 4 hours.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein the compound A is
Y1、Y2Are all Cl.
Preparation step S2:
under the condition of stirring, 20g of a compound II and a reaction solvent dichloromethane are added into a 1L drying reactor, an oxidation reagent potassium permanganate is added, the molar ratio of the compound II to the oxidation reagent is 1:3 respectively, the temperature of a reaction oil bath is 65 ℃, the reaction pressure is-0.01 MPa (gauge pressure), and the reaction time is 6 h.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 64%.
Preparation step S3:
under the drying condition, the crude product of the tris (hydroxymethyl) methylglycine obtained in the preparation step S2 is dissolved in a mixture of a purification solvent ethanol and water by using a drying closed device, then recrystallization is carried out, and crystallization, filtration and drying are carried out under the low-temperature condition, so as to obtain the refined tris (hydroxymethyl) methylglycine product with the purity of 99.5%.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
example 5
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of a mixture of compound I, tris (hydroxymethyl) aminomethane, compound A, a reaction solvent methanol and water was added to a 1L dry reactor, the molar ratio of compound I to compound A was 1:2, the reaction oil bath temperature was 60 ℃, the reaction pressure was 0MPa (gauge pressure), and the reaction time was 4 hours.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein, the compound A is sodium bromoacetate.
Preparation step S2:
under the condition of stirring, 20g of compound II is added into a 1L drying reactor, and after acid-base treatment reaction, sodium salt is changed into corresponding acid, the temperature of a reaction oil bath is 65 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 6 h.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 93%.
Preparation step S3:
under the drying condition, the crude product of the tris (hydroxymethyl) methylglycine obtained in the preparation step S2 is dissolved in a mixture of a purification solvent methanol and water by using a drying closed device, then recrystallization is carried out, and crystallization, filtration and drying are carried out under the low-temperature condition, so as to obtain the refined tris (hydroxymethyl) methylglycine product with the purity of 99.6%.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
example 6
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of compound I, trihydroxymethyl aminomethane, compound A and reaction solvent methanol are added into a 1L drying reactor, the molar ratio of the compound I to the compound A is 1:1 respectively, the temperature of a reaction oil bath is 60 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 4 h.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein, the compound A is ethyl ester corresponding to chloroacetic acid.
Preparation step S2:
under the condition of stirring, 20g of compound II is added into a 1L drying reactor, and after acid-base treatment reaction, ester is converted into corresponding acid, the temperature of a reaction oil bath is 65 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 6 h.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 92%.
Preparation step S3:
under the drying condition, the tris (hydroxymethyl) methylglycine of the crude product obtained in the preparation step S2 is dissolved in a purification solvent ethanol by using a drying closed device, then recrystallization is carried out, crystallization, filtration and drying are carried out under the low temperature condition, and the refined tris (hydroxymethyl) methylglycine refined product with the purity of 99.5 percent is obtained.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
example 7
A preparation method of tris (hydroxymethyl) methylglycine comprises the following preparation steps:
preparation step S1:
under the condition of stirring, 20g of compound I, trihydroxymethyl aminomethane, compound A and reaction solvent ethanol are added into a 1L drying reactor, the molar ratio of the compound I to the compound A is respectively 1:3, the temperature of a reaction oil bath is 60 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 4 h.
Cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude compound II;
wherein, the compound A is a mixture of paraformaldehyde and cyanide NaCN.
Preparation step S2:
under the condition of stirring, 20g of the compound II and a reaction solvent ethanol are added into a 1L drying reactor, water is added, hydrolysis reaction is carried out on the compound II and the water, the temperature of a reaction oil bath is 95 ℃, the reaction pressure is 0MPa (gauge pressure), and the reaction time is 6 h.
And (3) cooling to normal temperature after the reaction is finished, filtering to remove insoluble substances, performing rotary evaporation on the filtrate under reduced pressure to remove the solvent, and concentrating to obtain a crude product of the tris (hydroxymethyl) methylglycine, wherein the yield of the crude product is 52%.
Preparation step S3:
under the drying condition, the tris (hydroxymethyl) methylglycine of the crude product obtained in the preparation step S2 is dissolved in a purification solvent ethanol by using a drying closed device, then recrystallization is carried out, crystallization, filtration and drying are carried out under the low temperature condition, and the refined tris (hydroxymethyl) methylglycine refined product with the purity of 99.0 percent is obtained.
The nuclear magnetic resonance characterization data of the product is as follows:
1H NMR(400MHz，D2O)δ3.8ppm(6H)，3.7ppm(2H)。
the experiments show that the tris (hydroxymethyl) methylglycine prepared in the embodiment has high purity and low impurity content, the yield of crude products can reach more than 94 percent at most, the purity of fine products can reach more than 99.5 percent, and the application requirements of biological buffers can be met.
The above embodiments are only preferred embodiments of the present invention, and the protection scope of the present invention is not limited thereby, and any insubstantial changes and substitutions made by those skilled in the art based on the present invention are within the protection scope of the present invention.
Claims (11)
1. A preparation method of tris (hydroxymethyl) methylglycine is characterized by comprising the following preparation steps:
preparation step S1: reacting the compound I with the compound A to obtain a compound II;
preparation step S2: carrying out at least one reaction of hydrolysis reaction, oxidation reaction and acid-base treatment reaction on the compound II to obtain tri (hydroxymethyl) methylglycine;
wherein, the compound I is trihydroxymethyl aminomethane;
the compound A is
Or a salt thereof,
Or a salt thereof,
Or a salt thereof,
Y is halogen, OH, SH, ester corresponding to OH and ester corresponding to SH.
2. The process for producing tris (hydroxymethyl) methylglycine according to claim 1, characterised in that compound a is
At least one of, the Y1、Y2Are halogen, OH, SH, esters corresponding to OH and esters corresponding to SH.
3. The process according to claim 1, wherein compound a is at least one of bromoacetic acid, an ester of bromoacetic acid, an anhydride of bromoacetic acid, a mixed anhydride of bromoacetic acid, a bromoacetate salt, iodoacetic acid, an ester of iodoacetic acid, an anhydride of iodoacetic acid, a mixed anhydride of iodoacetic acid, and an iodoacetate salt.
4. The method according to claim 1, wherein the compound A is at least one selected from an ester corresponding to chloroacetic acid, an anhydride corresponding to chloroacetic acid, and a mixed anhydride corresponding to chloroacetic acid.
5. The method of claim 1, wherein the compound A is at least one of formaldehyde, paraformaldehyde, cyanuric acid, and cyanide MCN, and N is one of metal cation, inorganic ammonium cation, and organic amine cation.
6. The method for producing tris (hydroxymethyl) methylglycine according to any one of claims 1 to 4, characterized in that the ester mentioned in the compound A is at least one of a carboxylate, a sulfonate, a sulfinate, an inorganic acid ester; the salt mentioned in the compound A is at least one of metal salt, ammonium salt and complex salt based on acid-base action.
7. The method according to claim 1, wherein in step S2, the oxidizing agent used for oxidizing compound II is at least one selected from the group consisting of peroxide, ozone, permanganic acid, permanganate, dichromic acid, dichromate, hypochlorous acid, hypochlorite, chlorous acid, chlorite, fluorine gas, a mixed gas containing fluorine gas, chlorine gas, bromine, iodine, manganese dioxide, nitric acid, metachlorobenzoic acid, metachlorobenzoate, sulfuric acid, peroxymonosulfuric acid, peroxymonosulfate, dithionic acid, dithionate, pyrosulfuric acid, pyrosulfate, oxygen, caro' S acid, metachloroperbenzoic acid, metachloroperoxybenzoate, sulfur trioxide, and nitrogen dioxide.
8. The method according to claim 1, wherein in the step of S1, the molar ratio of compound I to compound a is 1: (0.1 to 10); in preparation step S2, the molar ratio of compound II to oxidizing agent is 1: (0.1-10).
9. The method for preparing tris (hydroxymethyl) methylglycine according to claim 1, wherein in the preparation step S1, the reaction temperature is-50 ℃ to 200 ℃, the reaction pressure is-0.05 MPa to 1MPa, and the reaction time is 0.1h to 72 h; in the preparation step S2, the reaction temperature is-50 ℃ to 200 ℃, the reaction pressure is-0.05 MPa to 1MPa, and the reaction time is 0.1h to 72 h.
10. The method according to claim 1, wherein in the step S1, compound I is reacted with compound a in a reaction solvent a, which is at least one selected from methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, water, and dimethylsulfoxide; in the preparation step S2, the compound II is reacted in a reaction solvent B, which is at least one of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, water, and dimethyl sulfoxide.
11. A process for the preparation of tris (hydroxymethyl) methylglycine according to any one of claims 1 to 10, characterised by the further preparation steps of:
under the dry condition, dissolving the crude product of the tris (hydroxymethyl) methylglycine obtained in the preparation step S2 in a purification solvent by using dry closed equipment or under the dry gas purging, then recrystallizing, crystallizing, filtering and drying under the low temperature condition to obtain refined tris (hydroxymethyl) methylglycine;
the purifying solvent is at least one of methanol, ethanol, acetone, tetrahydrofuran, ethyl acetate, dimethyl carbonate, diethyl ether, acetonitrile, dioxane, N-dimethylformamide, water and dimethyl sulfoxide.
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| JP2008066588A (en) * | 2006-09-08 | 2008-03-21 | Fujifilm Corp | Polishing solution |
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| CN108290849A (en) * | 2015-12-10 | 2018-07-17 | 伯拉考成像股份公司 | Contrast agent |
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| CN101402576B (en) * | 2008-10-23 | 2011-03-23 | 浙江大学 | Method for producing bi(2-hydroxyethyl)imino-tri(hydroxymethyl)methyl hydride |
| CN113861053B (en) * | 2021-09-26 | 2023-12-05 | 苏州亚科科技股份有限公司 | Preparation method of tris (hydroxymethyl) methylglycine |
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| SU642299A1 (en) * | 1977-09-26 | 1979-01-15 | Научно-производственное объединение "Биохимреактив" | Method of obtaining tricine |
| JP2008066588A (en) * | 2006-09-08 | 2008-03-21 | Fujifilm Corp | Polishing solution |
| CN103880691A (en) * | 2014-04-03 | 2014-06-25 | 重庆紫光国际化工有限责任公司 | Clean and environment-friendly production method of N,N-dialkylglycine |
| CN108290849A (en) * | 2015-12-10 | 2018-07-17 | 伯拉考成像股份公司 | Contrast agent |
| CN112194590A (en) * | 2020-10-16 | 2021-01-08 | 湖南韵邦生物医药有限公司 | Preparation method of tri (hydroxymethyl) methylglycine |
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| WO2023045601A1 (en) * | 2021-09-26 | 2023-03-30 | 苏州亚科科技股份有限公司 | Method for preparing tricine |
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